TY - JOUR
T1 - Membrane-type matrix metalloproteinase-1(MT1-MMP) gene is overexpressed in highly invasive hepatocellular carcinomas
AU - Harada, Tomika
AU - Arii, Shigeki
AU - Mise, Masahiro
AU - Imamura, Takashi
AU - Higashitsuji, Hiroaki
AU - Furutani, Masaharu
AU - Niwano, Mototaka
AU - Ishigami, Shun Ichi
AU - Fukumoto, Manabu
AU - Seiki, Motoharu
AU - Sato, Hiroshi
AU - Imamura, Masayuki
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1998/2
Y1 - 1998/2
N2 - Background/Aims: The matrix metalloproteinase (MMP) family play important roles in the invasion of cancer cells by degrading the extracellular matrices. The current study was designed to determine the expression pattern of membrane-type matrix metalloproteinase-1 (MT1-MMP) in hepatocellular carcinomas and its participation in invasion potential. Methods: MT1-MMP mRNA expression was examined in 25 human hepatocellular carcinoma specimens using Northern blot, and the correlation to clinicopathological features was evaluated. In situ hybridization and immunohistochemistry were performed to study the localization and the cells responsible for the production. Results: Northern blot analysis revealed high levels of MT1-MMP mRNA expression in tumorous portions in all cases, whereas in non-tumorous portions moderate or faint expression was evident in 22/25 cases. In 21/25 cases, the expression levels in tumorous portion were higher than those in non-tumorous portion. In particular, hepatocellular carcinoma with capsule infiltration demonstrated significantly higher expression than those without (p<0.05). In situ hybridization and immunohistochemical study revealed MT1-MMP transcripts and proteins in cancer cells and stromal cells, respectively. MT1-MMP positive cells were preferentially observed in the invading border of tumor nests. The MMP-2 transcript showed a similar pattern to that of MT1-MMP by in situ hybridization. Conclusion: The present study showed that the MT1-MMP gene is strongly expressed in hepatocellular carcinoma cells and is involved in the invasion potential of hepatocellular carcinoma, and also that MT1-MMP may be one of the key molecules responsible for the invasion potential of hepatocellular carcinoma. Furthermore, the evidence suggests that MT1-MMP and MMP-2 cooperate in the process of cancer invasion.
AB - Background/Aims: The matrix metalloproteinase (MMP) family play important roles in the invasion of cancer cells by degrading the extracellular matrices. The current study was designed to determine the expression pattern of membrane-type matrix metalloproteinase-1 (MT1-MMP) in hepatocellular carcinomas and its participation in invasion potential. Methods: MT1-MMP mRNA expression was examined in 25 human hepatocellular carcinoma specimens using Northern blot, and the correlation to clinicopathological features was evaluated. In situ hybridization and immunohistochemistry were performed to study the localization and the cells responsible for the production. Results: Northern blot analysis revealed high levels of MT1-MMP mRNA expression in tumorous portions in all cases, whereas in non-tumorous portions moderate or faint expression was evident in 22/25 cases. In 21/25 cases, the expression levels in tumorous portion were higher than those in non-tumorous portion. In particular, hepatocellular carcinoma with capsule infiltration demonstrated significantly higher expression than those without (p<0.05). In situ hybridization and immunohistochemical study revealed MT1-MMP transcripts and proteins in cancer cells and stromal cells, respectively. MT1-MMP positive cells were preferentially observed in the invading border of tumor nests. The MMP-2 transcript showed a similar pattern to that of MT1-MMP by in situ hybridization. Conclusion: The present study showed that the MT1-MMP gene is strongly expressed in hepatocellular carcinoma cells and is involved in the invasion potential of hepatocellular carcinoma, and also that MT1-MMP may be one of the key molecules responsible for the invasion potential of hepatocellular carcinoma. Furthermore, the evidence suggests that MT1-MMP and MMP-2 cooperate in the process of cancer invasion.
KW - Hepatocellular carcinoma
KW - Immunohistochemistry
KW - In situ hybridization
KW - MT1- MMP
KW - Northern blot
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U2 - 10.1016/0168-8278(88)80010-2
DO - 10.1016/0168-8278(88)80010-2
M3 - Article
C2 - 9514536
AN - SCOPUS:0032006647
VL - 28
SP - 231
EP - 239
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 2
ER -